ECHP_MOUSE
ID ECHP_MOUSE Reviewed; 718 AA.
AC Q9DBM2; Q91W49;
DT 24-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 4.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Peroxisomal bifunctional enzyme {ECO:0000305};
DE Short=PBE;
DE Short=PBFE;
DE AltName: Full=L-peroxisomal bifunctional enzyme {ECO:0000303|PubMed:24075987};
DE Short=L-PBE {ECO:0000303|PubMed:24075987};
DE AltName: Full=Multifunctional enzyme 1;
DE Short=MFE1;
DE AltName: Full=Multifunctional protein 1 {ECO:0000303|PubMed:17442273};
DE Short=MFP-1 {ECO:0000303|PubMed:17442273};
DE Includes:
DE RecName: Full=Enoyl-CoA hydratase/3,2-trans-enoyl-CoA isomerase;
DE EC=4.2.1.17 {ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
DE EC=5.3.3.8;
DE Includes:
DE RecName: Full=3-hydroxyacyl-CoA dehydrogenase;
DE EC=1.1.1.35 {ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
GN Name=Ehhadh {ECO:0000312|MGI:MGI:1277964};
GN Synonyms=L-pbe {ECO:0000303|PubMed:24075987};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17442273; DOI=10.1016/j.bbrc.2007.03.198;
RA Dirkx R., Meyhi E., Asselberghs S., Reddy J., Baes M., Van Veldhoven P.P.;
RT "Beta-oxidation in hepatocyte cultures from mice with peroxisomal gene
RT knockouts.";
RL Biochem. Biophys. Res. Commun. 357:718-723(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-543, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND SUBCELLULAR
RP LOCATION.
RX PubMed=24075987; DOI=10.1016/j.celrep.2013.08.032;
RA Ding J., Loizides-Mangold U., Rando G., Zoete V., Michielin O., Reddy J.K.,
RA Wahli W., Riezman H., Thorens B.;
RT "The peroxisomal enzyme L-PBE is required to prevent the dietary toxicity
RT of medium-chain fatty acids.";
RL Cell Rep. 5:248-258(2013).
RN [7]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-38; LYS-163; LYS-172; LYS-181;
RP LYS-189; LYS-217; LYS-240; LYS-252; LYS-274; LYS-278; LYS-288; LYS-329;
RP LYS-527; LYS-572; LYS-579; LYS-586; LYS-705 AND LYS-717, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-172; LYS-189; LYS-217; LYS-248;
RP LYS-274; LYS-344; LYS-348; LYS-355; LYS-459; LYS-579; LYS-586 AND LYS-705,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Peroxisomal trifunctional enzyme possessing 2-enoyl-CoA
CC hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-
CC CoA isomerase activities. Catalyzes two of the four reactions of the
CC long chain fatty acids peroxisomal beta-oxidation pathway
CC (PubMed:17442273, PubMed:24075987). Can also use branched-chain fatty
CC acids such as 2-methyl-2E-butenoyl-CoA as a substrate, which is
CC hydrated into (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA (By similarity).
CC Optimal isomerase for 2,5 double bonds into 3,5 form isomerization in a
CC range of enoyl-CoA species. Also able to isomerize both 3-cis and 3-
CC trans double bonds into the 2-trans form in a range of enoyl-CoA
CC species (By similarity). With HSD17B4, catalyzes the hydration of
CC trans-2-enoyl-CoA and the dehydrogenation of 3-hydroxyacyl-CoA, but
CC with opposite chiral specificity (Probable). Regulates the amount of
CC medium-chain dicarboxylic fatty acids which are essential regulators of
CC all fatty acid oxidation pathways (PubMed:24075987). Also involved in
CC the degradation of long-chain dicarboxylic acids through peroxisomal
CC beta-oxidation (By similarity). {ECO:0000250|UniProtKB:P07896,
CC ECO:0000250|UniProtKB:Q08426, ECO:0000269|PubMed:17442273,
CC ECO:0000269|PubMed:24075987, ECO:0000305|PubMed:24075987}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3S)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O;
CC Xref=Rhea:RHEA:16105, ChEBI:CHEBI:15377, ChEBI:CHEBI:57318,
CC ChEBI:CHEBI:58856; EC=4.2.1.17;
CC Evidence={ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16107;
CC Evidence={ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 4-saturated-(3S)-3-hydroxyacyl-CoA = a (3E)-enoyl-CoA + H2O;
CC Xref=Rhea:RHEA:20724, ChEBI:CHEBI:15377, ChEBI:CHEBI:58521,
CC ChEBI:CHEBI:137480; EC=4.2.1.17;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20725;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3Z)-enoyl-CoA = a 4-saturated (2E)-enoyl-CoA;
CC Xref=Rhea:RHEA:45900, ChEBI:CHEBI:85097, ChEBI:CHEBI:85489;
CC EC=5.3.3.8; Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45901;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3E)-enoyl-CoA = a 4-saturated (2E)-enoyl-CoA;
CC Xref=Rhea:RHEA:45228, ChEBI:CHEBI:58521, ChEBI:CHEBI:85097;
CC EC=5.3.3.8; Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45229;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:22432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57318,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726; EC=1.1.1.35;
CC Evidence={ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22433;
CC Evidence={ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S,3S)-3-hydroxy-2-methylbutanoyl-CoA = (2E)-2-methylbut-2-
CC enoyl-CoA + H2O; Xref=Rhea:RHEA:31119, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57312, ChEBI:CHEBI:57337;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31121;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-dodecenedioyl-CoA + H2O = (3S)-hydroxydodecanedioyl-CoA;
CC Xref=Rhea:RHEA:39075, ChEBI:CHEBI:15377, ChEBI:CHEBI:76340,
CC ChEBI:CHEBI:76342; Evidence={ECO:0000269|PubMed:24075987};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39076;
CC Evidence={ECO:0000269|PubMed:24075987};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxydodecanedioyl-CoA + NAD(+) = 3-oxododecanedioyl-
CC CoA + H(+) + NADH; Xref=Rhea:RHEA:39079, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:76342,
CC ChEBI:CHEBI:76346; Evidence={ECO:0000269|PubMed:24075987};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39080;
CC Evidence={ECO:0000269|PubMed:24075987};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-octenedioyl-CoA + H2O = (3S)-hydroxyoctanedioyl-CoA;
CC Xref=Rhea:RHEA:22532, ChEBI:CHEBI:15377, ChEBI:CHEBI:76330,
CC ChEBI:CHEBI:76333; Evidence={ECO:0000269|PubMed:17442273,
CC ECO:0000269|PubMed:24075987};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22533;
CC Evidence={ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyoctanedioyl-CoA + NAD(+) = 3-oxooctanedioyl-CoA +
CC H(+) + NADH; Xref=Rhea:RHEA:22848, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:76333,
CC ChEBI:CHEBI:76335; Evidence={ECO:0000269|PubMed:17442273,
CC ECO:0000269|PubMed:24075987};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22849;
CC Evidence={ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-decenedioyl-CoA + H2O = (3S)-hydroxydecanedioyl-CoA;
CC Xref=Rhea:RHEA:39091, ChEBI:CHEBI:15377, ChEBI:CHEBI:76347,
CC ChEBI:CHEBI:76348; Evidence={ECO:0000269|PubMed:24075987};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39092;
CC Evidence={ECO:0000269|PubMed:24075987};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxydecanedioyl-CoA + NAD(+) = 3-oxodecanedioyl-CoA +
CC H(+) + NADH; Xref=Rhea:RHEA:39095, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:76348,
CC ChEBI:CHEBI:76349; Evidence={ECO:0000269|PubMed:24075987};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39096;
CC Evidence={ECO:0000269|PubMed:24075987};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-tetradecenedioyl-CoA + H2O = (3S)-
CC hydroxytetradecanedioyl-CoA; Xref=Rhea:RHEA:40207, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:77038, ChEBI:CHEBI:77039;
CC Evidence={ECO:0000269|PubMed:17442273};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40208;
CC Evidence={ECO:0000269|PubMed:17442273};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxytetradecanedioyl-CoA + NAD(+) = 3-
CC oxotetradecanedioyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:40211,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:77038, ChEBI:CHEBI:77041;
CC Evidence={ECO:0000269|PubMed:17442273};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40212;
CC Evidence={ECO:0000269|PubMed:17442273};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E,5Z)-tetradecadienoyl-CoA = (2E,5Z)-tetradecadienoyl-CoA;
CC Xref=Rhea:RHEA:47464, ChEBI:CHEBI:71586, ChEBI:CHEBI:87701;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:47466;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E,5Z)-octadienoyl-CoA = (2E,5Z)-octadienoyl-CoA;
CC Xref=Rhea:RHEA:49932, ChEBI:CHEBI:85108, ChEBI:CHEBI:131990;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:49934;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxydecanoyl-CoA + NAD(+) = 3-oxodecanoyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:31187, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:62548, ChEBI:CHEBI:62616;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31188;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E)-decenoyl-CoA = (2E)-decenoyl-CoA; Xref=Rhea:RHEA:45752,
CC ChEBI:CHEBI:61406, ChEBI:CHEBI:84793;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45753;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3Z)-hexenoyl-CoA = (2E)-hexenoyl-CoA; Xref=Rhea:RHEA:45748,
CC ChEBI:CHEBI:62077, ChEBI:CHEBI:85415;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45749;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E)-hexenoyl-CoA = (2E)-hexenoyl-CoA; Xref=Rhea:RHEA:45736,
CC ChEBI:CHEBI:62077, ChEBI:CHEBI:84790;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45737;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxydecanoyl-CoA = (2E)-decenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:31191, ChEBI:CHEBI:15377, ChEBI:CHEBI:61406,
CC ChEBI:CHEBI:62616; Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31193;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexanoyl-CoA = (2E)-hexenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:30547, ChEBI:CHEBI:15377, ChEBI:CHEBI:62075,
CC ChEBI:CHEBI:62077; Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30549;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA
CC + H(+) + NADH; Xref=Rhea:RHEA:31159, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:62613; Evidence={ECO:0000250|UniProtKB:Q08426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31160;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanoyl-CoA = (2E)-hexadecenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:31163, ChEBI:CHEBI:15377, ChEBI:CHEBI:61526,
CC ChEBI:CHEBI:62613; Evidence={ECO:0000250|UniProtKB:Q08426};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31165;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-hexadecenedioyl-CoA + H2O = (3S)-hydroxyhexadecanedioyl-
CC CoA; Xref=Rhea:RHEA:40259, ChEBI:CHEBI:15377, ChEBI:CHEBI:77075,
CC ChEBI:CHEBI:77080; Evidence={ECO:0000250|UniProtKB:Q08426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40260;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanedioyl-CoA + NAD(+) = 3-
CC oxohexadecanedioyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:40267,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:77080, ChEBI:CHEBI:77081;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40268;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC -!- ACTIVITY REGULATION: Enzyme activity enhanced by acetylation.
CC {ECO:0000250|UniProtKB:Q08426}.
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P07896}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000305|PubMed:24075987}.
CC -!- PTM: Acetylated, leading to enhanced enzyme activity. Acetylation is
CC enhanced by up to 80% after treatment either with trichostin A (TCA) or
CC with nicotinamide (NAM) with highest increase on Lys-344. Acetylation
CC and enzyme activity increased by about 1.5% on addition of fatty acids
CC (By similarity). {ECO:0000250|UniProtKB:Q08426}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice fed a normal chow are phenotypically
CC indistinguishable from wild-types. Mutant mice fed coconut oil rapidly
CC lose weight and most of them die within 3 weeks. They overaccumulate
CC dicarboxylic fatty acids, which activate all fatty acid oxidation
CC pathways and lead to liver inflammation, fibrosis, and death.
CC {ECO:0000269|PubMed:24075987}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the enoyl-CoA
CC hydratase/isomerase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the 3-hydroxyacyl-CoA
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; AK004867; BAB23628.1; -; mRNA.
DR EMBL; BC016899; AAH16899.1; -; mRNA.
DR EMBL; CH466521; EDK97607.1; -; Genomic_DNA.
DR CCDS; CCDS28063.1; -.
DR RefSeq; NP_076226.2; NM_023737.3.
DR AlphaFoldDB; Q9DBM2; -.
DR SMR; Q9DBM2; -.
DR BioGRID; 216525; 16.
DR IntAct; Q9DBM2; 1.
DR MINT; Q9DBM2; -.
DR STRING; 10090.ENSMUSP00000023559; -.
DR SwissLipids; SLP:000000402; -.
DR SwissLipids; SLP:000000491; -.
DR iPTMnet; Q9DBM2; -.
DR PhosphoSitePlus; Q9DBM2; -.
DR SwissPalm; Q9DBM2; -.
DR EPD; Q9DBM2; -.
DR jPOST; Q9DBM2; -.
DR MaxQB; Q9DBM2; -.
DR PaxDb; Q9DBM2; -.
DR PeptideAtlas; Q9DBM2; -.
DR PRIDE; Q9DBM2; -.
DR ProteomicsDB; 277754; -.
DR Antibodypedia; 33832; 342 antibodies from 30 providers.
DR DNASU; 74147; -.
DR Ensembl; ENSMUST00000023559; ENSMUSP00000023559; ENSMUSG00000022853.
DR GeneID; 74147; -.
DR KEGG; mmu:74147; -.
DR UCSC; uc007yrm.2; mouse.
DR CTD; 1962; -.
DR MGI; MGI:1277964; Ehhadh.
DR VEuPathDB; HostDB:ENSMUSG00000022853; -.
DR eggNOG; KOG1683; Eukaryota.
DR GeneTree; ENSGT00940000157516; -.
DR HOGENOM; CLU_009834_16_3_1; -.
DR InParanoid; Q9DBM2; -.
DR OMA; TGAGWPF; -.
DR OrthoDB; 219667at2759; -.
DR PhylomeDB; Q9DBM2; -.
DR TreeFam; TF316708; -.
DR Reactome; R-MMU-390247; Beta-oxidation of very long chain fatty acids.
DR Reactome; R-MMU-9033241; Peroxisomal protein import.
DR UniPathway; UPA00659; -.
DR BioGRID-ORCS; 74147; 3 hits in 74 CRISPR screens.
DR PRO; PR:Q9DBM2; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q9DBM2; protein.
DR Bgee; ENSMUSG00000022853; Expressed in right kidney and 193 other tissues.
DR Genevisible; Q9DBM2; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0004165; F:delta(3)-delta(2)-enoyl-CoA isomerase activity; ISS:UniProtKB.
DR GO; GO:0004300; F:enoyl-CoA hydratase activity; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0016863; F:intramolecular oxidoreductase activity, transposing C=C bonds; ISS:UniProtKB.
DR GO; GO:0016509; F:long-chain-3-hydroxyacyl-CoA dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
DR GO; GO:0006637; P:acyl-CoA metabolic process; TAS:MGI.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IMP:MGI.
DR InterPro; IPR006180; 3-OHacyl-CoA_DH_CS.
DR InterPro; IPR006176; 3-OHacyl-CoA_DH_NAD-bd.
DR InterPro; IPR006108; 3HC_DH_C.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR018376; Enoyl-CoA_hyd/isom_CS.
DR InterPro; IPR001753; Enoyl-CoA_hydra/iso.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00725; 3HCDH; 2.
DR Pfam; PF02737; 3HCDH_N; 1.
DR Pfam; PF00378; ECH_1; 1.
DR SUPFAM; SSF48179; SSF48179; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52096; SSF52096; 1.
DR PROSITE; PS00067; 3HCDH; 1.
DR PROSITE; PS00166; ENOYL_COA_HYDRATASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Fatty acid metabolism; Isomerase; Lipid metabolism; Lyase;
KW Multifunctional enzyme; NAD; Oxidoreductase; Peroxisome; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..718
FT /note="Peroxisomal bifunctional enzyme"
FT /id="PRO_0000109248"
FT REGION 1..280
FT /note="Enoyl-CoA hydratase / isomerase"
FT REGION 281..567
FT /note="3-hydroxyacyl-CoA dehydrogenase"
FT MOTIF 716..718
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000250"
FT BINDING 99
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 102
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT SITE 122
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT MOD_RES 38
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 163
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q08426"
FT MOD_RES 163
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 172
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 172
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 181
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 189
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 189
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 217
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 217
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 240
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 248
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 252
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 274
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 274
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 278
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 288
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 329
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 344
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 348
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 355
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 459
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 527
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 543
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 572
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 579
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 579
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 586
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 586
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 705
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 705
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 717
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 499
FT /note="D -> G (in Ref. 1; BAB23628)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 718 AA; 78301 MW; A405717EC7A3EBD9 CRC64;
MAEYLRLPHS LAMIRLCNPP VNAISPTVIT EVRNGLQKAS LDHTVRAIVI CGANDNFCAG
ADIHGFKSPT GLTLGSLVDE IQRYQKPVVA AIQGVALGGG LELALGCHYR IANAKARVGF
PEVMLGILPG ARGTQLLPRV VGVPVALDLI TSGRHISTDE ALKLGILDVV VKSDPVEEAI
KFAQTVIGKP IEPRRILNKP VPSLPNMDSV FAEAIAKVRK QYPGRLAPET CVRSVQASVK
HPYEVAIKEE AKLFMYLRGS GQARALQYAF FAEKSANKWS TPSGASWKTA SAQPVSSVGV
LGLGTMGRGI AISFARVGIP VVAVESDPKQ LDTAKKIITS TLEKEASKSG QASAKPNLRF
SSSTKELSSV DLVIEAVFED MNLKKKVFAE LSALCKPGAF LCTNTSALDV DDIASSTDRP
QLVIGTHFFS PAHIMRLLEV IPSRYSSPTT IATVMSLSKR IGKIGVVVGN CYGFVGNRML
APYYNQGYFL IEEGSKPEDV DGVLEEFGFR MGPFRVSDLA GLDVGWKVRK GQGLTGPSLP
PGTPTRKRGN TRYSPIADML CEAGRFGQKT GKGWYQYDKP LGRIHKPDPW LSEFLSQYRE
THHIKQRSIS KEEILERCLY SLINEAFRIL EEGMAASPEH IDVIYLHGYG WPRHVGGPMY
YAASVGLPTV LEKLQKYYRQ NPDIPQLEPS DYLRRLVAQG SPPLKEWQSL AGPHSSKL
